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CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.
Province, M A; Goetz, M P; Brauch, H; Flockhart, D A; Hebert, J M; Whaley, R; Suman, V J; Schroth, W; Winter, S; Zembutsu, H; Mushiroda, T; Newman, W G; Lee, M-T M; Ambrosone, C B; Beckmann, M W; Choi, J-Y; Dieudonné, A-S; Fasching, P A; Ferraldeschi, R; Gong, L; Haschke-Becher, E; Howell, A; Jordan, L B; Hamann, U; Kiyotani, K; Krippl, P; Lambrechts, D; Latif, A; Langsenlehner, U; Lorizio, W; Neven, P; Nguyen, A T; Park, B-W; Purdie, C A; Quinlan, P; Renner, W; Schmidt, M; Schwab, M; Shin, J-G; Stingl, J C; Wegman, P; Wingren, S; Wu, A H B; Ziv, E; Zirpoli, G; Thompson, A M; Jordan, V C; Nakamura, Y; Altman, R B; Ames, M M.
Afiliação
  • Province MA; Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Goetz MP; Department of Oncology and Pharmacology, Mayo Clinic, Rochester, Minnesota, USA.
  • Brauch H; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University, Tuebingen, Germany.
  • Flockhart DA; Division of Clinical Pharmacology, School of Medicine, Indiana University, Bloomington, Indiana, USA.
  • Hebert JM; Department of Genetics, School of Medicine, Stanford University, Stanford, California, USA.
  • Whaley R; Department of Genetics, School of Medicine, Stanford University, Stanford, California, USA.
  • Suman VJ; Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
  • Schroth W; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University, Tuebingen, Germany.
  • Winter S; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University, Tuebingen, Germany.
  • Zembutsu H; Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Mushiroda T; Laboratory for Pharmacogenetics, RIKEN Center for Genomic Medicine, Yokohama, Japan.
  • Newman WG; Centre for Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
  • Lee MT; Laboratory for International Alliance, RIKEN Center for Genomic Medicine, Yokohama, Japan.
  • Ambrosone CB; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, USA.
  • Beckmann MW; Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Choi JY; Department of Biomedical Science, Graduate School, Seoul National University, Seoul, Korea.
  • Dieudonné AS; Department of Oncology, Catholic University Leuven, Leuven, Belgium.
  • Fasching PA; 1] Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany [2] Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, Californi
  • Ferraldeschi R; Centre for Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
  • Gong L; Department of Genetics, School of Medicine, Stanford University, Stanford, California, USA.
  • Haschke-Becher E; University Institute of Medical and Chemical Laboratory Diagnostics, Paracelsus Private Medical University, Salzburg, Austria.
  • Howell A; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
  • Jordan LB; Department of Pathology, Ninewells Hospital and Medical School, Dundee, UK.
  • Hamann U; Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
  • Kiyotani K; Laboratory for Pharmacogenetics, RIKEN Center for Genomic Medicine, Yokohama, Japan.
  • Krippl P; Medical University Graz, Graz, Austria.
  • Lambrechts D; Vesalius Research Center, VIB and Laboratory of Translational Genetics, Department of Oncology, Catholic University Leuven, Leuven, Belgium.
  • Latif A; Centre for Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
  • Langsenlehner U; Medical University Graz, Graz, Austria.
  • Lorizio W; Division of General Internal Medicine, Department of Medicine and Clinical Pharmacology and Experimental Therapeutics, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Neven P; Department of Gynecology and Obstetrics, University Hospitals Leuven, Leuven, Belgium.
  • Nguyen AT; Division of Clinical Pharmacology, School of Medicine, Indiana University, Bloomington, Indiana, USA.
  • Park BW; Department of Surgery, Yonsei University Health System, Seoul, Korea.
  • Purdie CA; Department of Pathology, Ninewells Hospital and Medical School, Dundee, UK.
  • Quinlan P; Dundee Cancer Centre, Dundee, UK.
  • Renner W; Medical University Graz, Graz, Austria.
  • Schmidt M; 1] Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University, Tuebingen, Germany [2] Department of Gynecology and Obstetrics, University of Mainz, Mainz, Germany.
  • Schwab M; Department of Clinical Pharmacology and Toxicology, University Hospital Tuebingen, Tuebingen, Germany.
  • Shin JG; 1] Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan, Korea [2] Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Korea.
  • Stingl JC; Division of Research, Federal Institute for Drugs and Medical Devices, University of Bonn Medical Faculty, Bonn, Germany.
  • Wegman P; Department of Clinical Medicine, Ö rebro University, Örebro, Sweden.
  • Wingren S; Department of Clinical Medicine, Ö rebro University, Örebro, Sweden.
  • Wu AH; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Ziv E; Division of General Internal Medicine, Department of Medicine and Clinical Pharmacology and Experimental Therapeutics, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Zirpoli G; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, USA.
  • Thompson AM; Dundee Cancer Centre, Dundee, UK.
  • Jordan VC; Department of Oncology, Georgetown University, Washington, DC, USA.
  • Nakamura Y; Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Altman RB; 1] Department of Genetics, School of Medicine, Stanford University, Stanford, California, USA [2] Department of Bioengineering, Stanford University, Stanford, California, USA.
  • Ames MM; Department of Pharmacology, Mayo Clinic, Rochester, Minnesota, USA.
Clin Pharmacol Ther ; 95(2): 216-27, 2014 Feb.
Article em En | MEDLINE | ID: mdl-24060820
ABSTRACT
The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tamoxifeno / Neoplasias da Mama / Antineoplásicos Hormonais / Citocromo P-450 CYP2D6 Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Aged / Female / Humans / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tamoxifeno / Neoplasias da Mama / Antineoplásicos Hormonais / Citocromo P-450 CYP2D6 Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Aged / Female / Humans / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article